An Artificial Salivary Gland Tissue That Produces Natural Saliva

December 5, 20183 min read

Researchers created an artificial tissue that was very similar to real salivary glands.

The tissue functioned normally in mice without salivary glands.

Unfortunately, humans don’t have the incredible capability of regrowing organ when they lose it due to injury or disease. In animals, organogenesis is an important event during embryogenesis. It’s a complex process that goes until birth, and generally involves movements and interactions among cells.

Organogenesis involves unique stem cells that eventually become particular tissues. However, in some exceptional organs like hair follicles, these cells are only present during the initial growth phase.

On the other hand, induced pluripotent stem cells or embryonic stem cells are capable of transforming into several different kinds of cells to produce organoid – a miniaturized 3D multicellular tissue that resembles an actual organ. Developing functional organoid could be very useful for patients with organ failure. It could help patients recover some of those real organs functions.

Recently, scientists at RIKEN Center for Biosystems Dynamics Research and Showa University recreated a salivary gland tissue, which plays a crucial role in facilitating swallowing and digesting starch. Surprisingly, this tissue functioned normally in a living mammal.

Challenge of Creating An Organoid

The salivary glands form as epithelial buds in the oral cavity form 6th to 7th week, and it is mostly impaired by cancer radiation therapy or Sjogren’s syndrome, an immune system disorder.

The actual mechanism of salivary glands formation is still not well-explored yet. However, we do know that the development of organ is an extremely complex process that involves chemical signaling and alterations in gene expression.

In this work, researchers detected two transcription factors responsible for differentiating stem cells into salivary gland, i.e. Foxc1 and Sox9. They also detected a signaling chemical pair, named FGF10 and FGF7, that triggered cells expressing those transcription factors.

To create an artificial salivary gland, they used a chemical mixture for inducing embryonic stem cells and produce ectoderm. Then, with the help of viral vectors, they made cells express both Fox1 and Sox9. Putting 2 chemicals into the mixture triggered the cells to produce tissue that was quite identical to real salivary glands.

Schematic representation of the development of salivary gland | Courtesy of researchers

Testing

Would this salivary gland tissue actually work in a real mammal? To find the answer, researchers implanted those tissues (along with an embryonic connective tissue called mesenchyme) into mice without salivary glands and fed them critic acid.

They found that transplanted tissue was perfectly linked to the nerve tissue, and secreted a liquid (in response to the stimulation) that was very similar to actual saliva.

It’s a major proof of concept that real organs can be replaced by artificial organoids. Researchers plan to further grow functional tissues to replace several organs’ functions. They will study organ maturation factors for full functional organ replacement, contributing to the evolution of next-generation organ replacement regenerative therapy through pluripotent stem cells.